On the physiology of artificial hibernation

This thesis aims to translate insights from the physiology of natural hibernators to a model of artificial hibernation that could aid clinical applications. In Part I, the governing physiological elements that are responsible for the induction of (artificial) hibernation are discussed. Chapter 1 presents a model that identifies the necessary physiological changes for induction of artificial hibernation. Chapter 2 dives deeper into (bio)chemical and pharmacological agents with thermoregulatory properties. In Part II, the effects of a popular biochemical agent, hydrogen sulfide (H₂S), are evaluated for its potential to induce artificial hibernation in large and small animals. Chapter 3 starts with a series of experiments in large animals (pigs), studying the systemic effects of H₂S. Chapter 4 goes back to a small-animal model (mice) and compares the effects of H₂S to the more potent effects of hypoxia for the induction of artificial hibernation. Part III ends with a description of practical systems and strategies for bringing this model to single organ application in the liver. Chapter 5 describes the necessary preparations to the liver to maintain stable extracorporeal hepatic physiological function. The final chapter demonstrated how several of the model’s elements can be controlled in an extracorporeal environment.